Cited by 44RNA and protein synthesis mechanismsRNA Research and SplicingGenetics and Neurodevelopmental Disorders

Axonal endoplasmic reticulum tubules control local translation via P180/RRBP1-mediated ribosome interactions

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Koppers, Max, Özkan, Nazmiye, Nguyen, Ha H., Jurriens, Daphne, McCaughey, Janine, Nguyen, Dan T.M., Li, Chun Hei, Stucchi, Riccardo +5 more·2024·Developmental Cell

Published version of a preprint

Abstract

Local mRNA translation in axons is critical for the spatiotemporal regulation of the axonal proteome. A wide variety of mRNAs are localized and translated in axons; however, how protein synthesis is regulated at specific subcellular sites in axons remains unclear. Here, we establish that the axonal endoplasmic reticulum (ER) supports axonal translation in developing rat hippocampal cultured neurons. Axonal ER tubule disruption impairs local translation and ribosome distribution. Using nanoscale resolution imaging, we find that ribosomes make frequent contacts with axonal ER tubules in a translation-dependent manner and are influenced by specific extrinsic cues. We identify P180/RRBP1 as an axonally distributed ribosome receptor that regulates local translation and binds to mRNAs enriched for axonal membrane proteins. Importantly, the impairment of axonal ER-ribosome interactions causes defects in axon morphology. Our results establish a role for the axonal ER in dynamically localizing mRNA translation, which is important for proper neuron development.

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Crossref · 10.1016/j.devcel.2024.05.005

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Authors
Koppers, M., Özkan, N., Nguyen, H. H., Jurriens, D., McCaughey, J., Nguyen, D. T. M., Li, C. H., Stucchi, R., Altelaar, M., MacGillavry, H. D., Kapitein, L. C., Hoogenraad, C. C., & Farías, G. G.
Affiliations
  • Utrecht University (NL)
  • Genentech (US)
Corresponding author
Koppers, Max
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2024-08
Volume
59
Issue
16
Pages
2053-2068.e9
ISSN
1534-5807 (ISSN-L)
OpenAlex
W4399123356
Cited by
44
References
81
Citations by year
2026: 13 · 2025: 22 · 2024: 7 · 2023: 1 · 2022: 1
FWCI
5.72
Type
journal article
Language
en
Open access
Locations
  • Developmental Cell (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • VU Research Portal (submittedVersion, other-oa)
Funders
  • ERC (ERC-CoG 617050, ERC-CoG 819219, ERC-StG 950617)
  • EMBO
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VI.VENI.202.113, ALTF 741-2020)
  • European Research Council (0.16)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
ER tubules, ribosome distribution, axon development, axon morphology, hippocampal neurons, neuronal development
MeSH terms
Animals, Axons, Carrier Proteins, Cells, Cultured, Endoplasmic Reticulum, Hippocampus, Humans, Neurons, Ribosomal Proteins, Ribosomes, RNA, Messenger, Protein Biosynthesis, Rats

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